c4oh -肉碱：有或无先天性代谢错误患者酮症的重要标志物

IF 3.5 2区生物学 Q2 ENDOCRINOLOGY & METABOLISM

Molecular genetics and metabolism Pub Date : 2025-06-02 DOI:10.1016/j.ymgme.2025.109160

Maria Laura Duque Lasio , Maria Zaitsev , Judith A. Hobert , Irene De Biase , Marzia Pasquali , Tatiana Yuzyuk

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引用次数: 0

摘要

C4OH（3-羟基丁基- /3-羟基异丁基-）肉碱升高已被报道在生理性酮症中，继发于生酮饮食，并且在几种先天性代谢错误（IEMs）中也被观察到。然而，血浆c4oh -肉碱作为常规酰基肉碱检测酮症标志物的可靠性尚未得到广泛研究。本研究的目的是将血浆c4oh -肉碱水平与血浆/血清β-羟基丁酸（BHB）的测量相关联。我们还调查了不同疾病中c4oh -肉碱升高的发生率。方法对送到实验室进行血浆酰基肉碱分析的75000份样品进行回顾性分析。559份样品中c4oh -肉碱和BHB浓度存在相关性，同时存在BHB和酰基肉碱谱。在提交给酰基肉碱分析的151个样品中也直接测量了BHB。在2000例已知诊断为IEM的患者样本中评估c4oh -肉碱浓度的范围和c4oh -肉碱升高的频率。结果c4oh -肉毒碱与BHB浓度有较强的相关性(Spearman系数r >；0.80, p <；0.0001)。c4oh -肉碱与BHB分析结果的总体一致性为84%，阴性预测值为74%，阳性预测值为96%。在IEM队列中，在l- 3-羟基酰基辅酶a脱氢酶缺乏症患者中，c4oh -肉碱持续升高。β -酮硫酶缺乏症、甲基丙二酸血症（MMA）和丙酸血症（PA）患者的大量样本中c4oh -肉碱含量较高（分别为35%、21%和17%），反映酮症。c4oh -肉碱异常在多重酰基辅酶a脱氢酶缺乏症（7.7%）、超长链酰基辅酶a脱氢酶缺乏症（VLCADD, 5.8%）、戊二酸血症1型（4.6%）和中链酰基辅酶a脱氢酶缺乏症（0.4%）中较少见。即使校正了游离肉碱，在c4oh -肉碱升高的MMA、PA和VLCADD样品中，诊断性酰基肉碱种类的浓度也明显高于c4oh -肉碱正常的样品。结论血浆c4oh -肉碱浓度与血浆/血清BHB浓度呈正相关，提示c4oh -肉碱升高是酮症的可靠标志物。IEMs患者c4oh -肉碱升高可能表明代谢状态，应提示额外的代谢和营养评估，以防止代谢失代偿。

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C4OH-carnitine: an important marker of ketosis in patients with and without inborn errors of metabolism

Background

Elevated C4OH (3-hydroxybutyryl−/3-hydroxyisobutyryl-) carnitine has been reported in physiologic ketosis, secondary to ketogenic diet, and is also observed in several Inborn Errors of Metabolism (IEMs). However, the reliability of plasma C4OH-carnitine as a marker of ketosis on routine acylcarnitine testing has not been extensively studied. The goal of this study was to correlate the plasma C4OH-carnitine levels with the measurements of plasma/serum β-hydroxybutyrate (BHB). We also investigated the prevalence of elevated C4OH-carnitine in different IEMs.

Methods

We conducted a retrospective analysis of >75,000 samples sent to our laboratory for plasma acylcarnitine analysis. The concentrations of C4OH-carnitine and BHB were correlated in 559 samples with concurrent BHB and acylcarnitine profile (ACP). BHB was also directly measured in 151 samples submitted for acylcarnitine analysis. The range of C4OH-carnitine concentrations and the frequency of elevated C4OH-carnitine was evaluated in >2000 samples from patients with known diagnosis of IEM.

Results

We observed a strong correlation between C4OH-carnitine and BHB concentration (Spearman coefficient r > 0.80, p < 0.0001). The overall concordance between C4OH-carnitine and BHB results in analyzed samples was 84 % with negative and positive predictive values of 74 % and 96 %, respectively. In the IEM cohort, isolated elevations of C4OH-carnitine were consistently present in a patient with L-3-hydroxyacyl-CoA dehydrogenase deficiency. A large number of samples from patients with beta-ketothiolase deficiency, methylmalonic acidemia (MMA) and propionic acidemia (PA) had high C4OH-carnitine (35 %, 21 % and 17 %, respectively) reflecting ketosis. Abnormal C4OH-carnitine was less commonly seen in multiple acyl-CoA dehydrogenase deficiency (7.7 %), very long-chain acyl-CoA dehydrogenase deficiency (VLCADD, 5.8 %), glutaric acidemia type 1 (4.6 %), and medium-chain acyl-CoA dehydrogenase deficiency (0.4 %). Significantly higher concentrations of diagnostic acylcarnitine species were observed in MMA, PA and VLCADD samples with elevated C4OH-carnitine vs samples with normal C4OH-carnitine even after correcting for free carnitine.

Conclusion

Plasma C4OH-carnitine concentration showed a strong positive correlation with plasma/serum concentrations of BHB, demonstrating that elevated C4OH-carnitine is a reliable marker of ketosis. Elevated C4OH-carnitine in individuals with IEMs could indicate catabolic state and should prompt additional metabolic and nutritional evaluations to prevent metabolic decompensation.

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来源期刊

Molecular genetics and metabolism 生物-生化与分子生物学

CiteScore

5.90

自引率

7.90%

发文量

621

审稿时长

34 days

期刊介绍： Molecular Genetics and Metabolism contributes to the understanding of the metabolic and molecular basis of disease. This peer reviewed journal publishes articles describing investigations that use the tools of biochemical genetics and molecular genetics for studies of normal and disease states in humans and animal models.